API

Event: 1116

Key Event Title

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Decreased, Triiodothyronine (T3) in tissues

Short name

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Decreased, Triiodothyronine (T3) in tissues

Biological Context

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Level of Biological Organization
Tissue


Organ term

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Key Event Components

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Process Object Action
3,3',5-triiodo-L-thyronine increased
3,3',5-triiodo-L-thyronine decreased

Key Event Overview


AOPs Including This Key Event

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Stressors

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Taxonomic Applicability

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Term Scientific Term Evidence Link
African clawed frog Xenopus laevis High NCBI

Life Stages

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Life stage Evidence
Development Moderate

Sex Applicability

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Term Evidence
Unspecific Moderate

Key Event Description

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In many ways, this key event fundamentally works the same as key event 1093: Thyroxine (T4) in tissues, decreased. However, T3 can only exist in tissues from either direct uptake from the serum or produced locally from outer ring deiodination (ORD) of T4. ORD of T4 can occur in any tissue that expresses either type I or II iodothyronine deiodinases (DIO1, DIO2). Although T3 can be produced in peripheral tissues from T4 via ORD, T4 can only be synthesized in the thyroid gland. The local concentration of T3 in any given cell or tissue will be a function of, (1) local T4 availability, which is a function of plasma T4 concentration and active transport capacity across cell membranes, (2) local DIO1 and/or DIO2 activity, and (3) circulating levels of T3, as a result of remote activation of T4 by either DIO1 or DIO2 and release of T3 to the plasma.


How It Is Measured or Detected

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This key event is measured the same as key event 1093: Thyroxine (T4) in tissues, decreased. Summary table of measurement methods.


Domain of Applicability

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The essentiality of this key event applies during thyroid-mediated metamorphosis in amphibians and especially African clawed frog (Xenopus laevis), which provides the basis for this key event leading to altered metamorphosis. However, direct measurements of this key event are not routine or typical. The support for this key event exists primarily as biological plausibility and thyroid endocrinology dogma.


Evidence for Perturbation by Stressor



Methimazole

Inferred given effect of reduced thyroid hormone synthesis on lack of metamorphic changes in tissues.


Propylthiouracil

Inferred given effect of reduced thyroid hormone synthesis on lack of metamorphic changes in tissues.


Mercaptobenzothiazole

Inferred given effect of reduced thyroid hormone synthesis on lack of metamorphic changes in tissues.


Perchlorate

Inferred given effect of reduced thyroid hormone synthesis on lack of metamorphic changes in tissues.


References

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Ackermans, M.T., Kettelarij‐Haas, Y., Boelen, A. and Endert, E., 2012. Determination of thyroid hormones and their metabolites in tissue using SPE UPLC‐tandem MS. Biomedical Chromatography, 26(4), pp.485-490.

Bastian, T.W., Prohaska, J.R., Georgieff, M.K. and Anderson, G.W., 2010. Perinatal iron and copper deficiencies alter neonatal rat circulating and brain thyroid hormone concentrations. Endocrinology, 151(8), pp.4055-4065.

Bastian, T.W., Anderson, J.A., Fretham, S.J., Prohaska, J.R., Georgieff, M.K. and Anderson, G.W., 2012. Fetal and neonatal iron deficiency reduces thyroid hormone-responsive gene mRNA levels in the neonatal rat hippocampus and cerebral cortex. Endocrinology, 153(11), pp.5668-5680.

Bastian, T.W., Prohaska, J.R., Georgieff, M.K. and Anderson, G.W., 2013. Fetal and neonatal iron deficiency exacerbates mild thyroid hormone insufficiency effects on male thyroid hormone levels and brain thyroid hormone-responsive gene expression. Endocrinology, 155(3), pp.1157-1167.

Crane, H.M., Pickford, D.B., Hutchinson, T.H. and Brown, J.A., 2004. Developmental changes of thyroid hormones in the fathead minnow, Pimephales promelas. General and comparative endocrinology, 139(1), pp.55-60.

Donzelli, R., Colligiani, D., Kusmic, C., Sabatini, M., Lorenzini, L., Accorroni, A., Nannipieri, M., Saba, A., Iervasi, G. and Zucchi, R., 2016. Effect of Hypothyroidism and Hyperthyroidism on Tissue Thyroid Hormone Concentrations in Rat. European thyroid journal, 5(1), pp.27-34.

ESCOBAR, G.M.D., Pastor, R., Obregón, M.J. and REY, F.E.D., 1985. Effects of Maternal Hypothyroidism on the Weight and Thyroid Hormone Content of Rat Embryonic Tissues, before and after Onset of Fetal Thyroid Function*. Endocrinology, 117(5), pp.1890-1900.

Gilbert, M.E., Hedge, J.M., Valentín-Blasini, L., Blount, B.C., Kannan, K., Tietge, J., Zoeller, R.T., Crofton, K.M., Jarrett, J.M. and Fisher, J.W., 2013. An animal model of marginal iodine deficiency during development: the thyroid axis and neurodevelopmental outcome. toxicological sciences, p.kfs335.

Hornung, M.W., Kosian, P.A., Haselman, J.T., Korte, J.J., Challis, K., Macherla, C., Nevalainen, E. and Degitz, S.J., 2015. In vitro, ex vivo, and in vivo determination of thyroid hormone modulating activity of benzothiazoles. Toxicological Sciences, 146(2), pp.254-264.

Kunisue, T., Fisher, J.W., Fatuyi, B. and Kannan, K., 2010. A method for the analysis of six thyroid hormones in thyroid gland by liquid chromatography–tandem mass spectrometry. Journal of Chromatography B, 878(21), pp.1725-1730.

Kunisue, T., Fisher, J.W. and Kannan, K., 2011. Determination of six thyroid hormones in the brain and thyroid gland using isotope-dilution liquid chromatography/tandem mass spectrometry. Analytical chemistry, 83(1), pp.417-424.

Lavado-Autric, R., Calvo, R.M., de Mena, R.M., de Escobar, G.M. and Obregon, M.J., 2012. Deiodinase activities in thyroids and tissues of iodine-deficient female rats. Endocrinology, 154(1), pp.529-536.

Pinna, G., Hiedra, L., Prengel, H., Broedel, O., Eravci, M., Meinhold, H. and Baumgartner, A., 1999. Extraction and quantification of thyroid hormones in selected regions and subcellular fractions of the rat brain. Brain Research Protocols, 4(1), pp.19-28.

Simon, R., Tietge, J., Michalke, B., Degitz, S. and Schramm, K.W., 2002. Iodine species and the endocrine system: thyroid hormone levels in adult Danio rerio and developing Xenopus laevis. Analytical and bioanalytical chemistry, 372(3), pp.481-485.

Saba, A., Donzelli, R., Colligiani, D., Raffaelli, A., Nannipieri, M., Kusmic, C., Dos Remedios, C.G., Simonides, W.S., Iervasi, G. and Zucchi, R., 2014. Quantification of thyroxine and 3, 5, 3′-triiodo-thyronine in human and animal hearts by a novel liquid chromatography-tandem mass spectrometry method. Hormone and Metabolic Research, 46(09), pp.628-634.

Tietge, J.E., Butterworth, B.C., Haselman, J.T., Holcombe, G.W., Hornung, M.W., Korte, J.J., Kosian, P.A., Wolfe, M. and Degitz, S.J., 2010. Early temporal effects of three thyroid hormone synthesis inhibitors in Xenopus laevis. Aquatic Toxicology, 98(1), pp.44-50.

Tietge, J.E., Degitz, S.J., Haselman, J.T., Butterworth, B.C., Korte, J.J., Kosian, P.A., Lindberg-Livingston, A.J., Burgess, E.M., Blackshear, P.E. and Hornung, M.W., 2013. Inhibition of the thyroid hormone pathway in Xenopus laevis by 2-mercaptobenzothiazole. Aquatic toxicology, 126, pp.128-136.